Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations.

ABSTRACT:

Purpose

Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease.

Methods

We identified major events in NPC1 evolution and revealed and compared

SUBMITTER: Adebali O 

PROVIDER: S-EPMC4990510 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature